Neonates are easily suffering from local or systematic infections due to their vulnerable skin barrier function, which leads to the increasing risk of death. Therefore, it is important to protect neonatal skin integrity and prevent neonatal skin injury in the neonatal intensive care unit (NICU). Based on Grading of Recommendations Assessment, Development and Evaluation (GRADE) and current evidence, the guidelines for neonatal skin management in the NICU were developed to provide recommendations on routine skin care and prevention and treatment of iatrogenic skin injury of neonates for health care providers.

Objective To study the efficacy and safety of lactase additive in improving lactose intolerance in preterm infants. Methods A total of 60 preterm infants with lactose intolerance who were admitted to the Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine from January 2018 to December 2019 were randomly divided into a lactase treatment group and a control group, with 30 infants in each group. The infants in the lactase treatment group were given 4 drops of lactase additive (180 mg) added into preterm formula or breast milk, and those in the control group were given placebo, oral administration of probiotics (live combined Bifidobacterium, Lactobacillus and Enterococcus powder) at half an hour after feeding (1 g each time, twice a day), and clockwise abdominal massage around the belly button at 1 hour after feeding for 15 minutes each time, 3 times a day. Fecal pH, fecal reducing sugar, growth indicators, symptoms of lactose intolerance, and laboratory markers were measured at the end of the first and second weeks after intervention. Results Finally 29 infants in the lactase treatment group and 26 infants in the control group completed the trial. At the end of the first week after intervention, compared with the control group, the lactase treatment group had significantly lower frequency of daily milk vomiting and gastric retention amount (P < 0.05) and a significantly higher proportion of infants with fecal pH > 5.0 (P < 0.05). At the end of the second week after intervention, compared with the control group, the lactase treatment group had significantly lower frequency of daily milk vomiting and 24-hour abdominal circumference difference (P < 0.05) and a significantly higher proportion of infants with the absence of gastric retention, fecal pH > 5.0, or negative reducing sugar in feces (P < 0.05). No adverse reactions associated with the lactase additive or probiotics were observed during the trial. Conclusions Lactase additive can safely and effectively improve the clinical symptoms caused by lactose intolerance in preterm infants.

Objective To study the characteristics of gut microbiota and its association with the activity of β-glucuronidase (β-GD) in neonates with hyperbilirubinemia. Methods A total of 50 neonates with hyperbilirubinemia who were admitted in January to December, 2018, were enrolled as the hyperbilirubinemia group, and 30 neonates without hyperbilirubinemia were enrolled as the control group. The 16S rRNA high-throughput sequencing method was used to compare gut microbiota between the two groups. The phenolphthalein-glucuronic acid substrate method was used to measure the activity of β-GD in the intestinal tract of neonates with hyperbilirubinemia before and after treatment. Results The comparison of the distribution of gut microbiota at the genus level showed a significant difference in the abundance of 52 bacteria between the hyperbilirubinemia and control groups before treatment (P < 0.05), as well as a significant difference in the abundance of 42 bacteria between the hyperbilirubinemia group on day 3 after treatment and the control group on day 3 after enrollment (P < 0.05). After treatment, the hyperbilirubinemia group had significant reductions in the content of Escherichia and Staphylococcus in the intestinal tract (P < 0.05) and the activity of β-GD in feces (P < 0.05). The activity of β-GD in feces was positively correlated with the abundance of Staphylococcus and Escherichia before and after treatment in the neonates with hyperbilirubinemia (r_s=0.5948-0.7245, P < 0.01). Conclusions There are differences in gut microbiota between the neonates with hyperbilirubinemia and those without hyperbilirubinemia. The activity of β-GD in feces is positively correlated with the abundance of Staphylococcus and Escherichia in neonates with hyperbilirubinemia. Gut microbiota may affect the development of neonatal hyperbilirubinemia by regulating the activity of β-GD. The determination and analysis of gut microbiota and β-GD activity may have certain clinical significance for the early assessment of the development of neonatal hyperbilirubinemia.

Objective To study the incidence and clinical features of sepsis in very low birth weight (VLBW) infants. Methods The clinical data were collected from VLBW infants, with a birth weight of < 1 500 g, who were admitted to the Department of Neonatology, Maternity Hospital Affiliated to Nanjing Medical University, from January 2019 to June 2020. The incidence of sepsis, distribution of pathogenic bacteria, and risk factors for sepsis were analyzed. Results A total of 369 infants were enrolled, and 138 infants had sepsis, among whom 84 had early-onset sepsis (EOS) and 54 had late-onset sepsis (LOS). Enterococcus faecalis (24%) and Streptococcus (21%) were the main pathogenic bacteria in infants with EOS, and Staphylococcus (41%) and Enterobacter (29%) were the main pathogenic bacteria in infants with LOS. The incidence of EOS and LOS decreased with the increase of gestational age and birth weight (P < 0.05). The multivariate logistic regression analysis showed that a high birth weight was a protective factor against EOS (OR=0.996, 95%CI:0.993-0.998, P < 0.05), while vaginal delivery (OR=2.781, 95%CI:1.190-6.500, P < 0.05) was a risk factor for EOS, and long duration of parenteral nutrition was a risk factor for LOS (OR=1.129, 95%CI:1.067-1.194, P < 0.05). Conclusions Enterococcus faecalis is the most common pathogenic bacteria for EOS, and Staphylococcus is the most common pathogenic bacterium for LOS in VLBW infants. A high birth weight may reduce the risk of EOS in VLBW infants, while vaginal delivery may increase the risk of EOS. Prolonged parenteral nutrition may increase the risk of LOS.

Objective To study the clinical features, treatment, and prognosis of neonates with Kasabach-Merritt syndrome (KMS), and to provide a reference for optimizing the diagnosis and treatment of this disease. Methods A retrospective analysis was performed for the clinical and follow-up data of 16 neonates with KMS who were admitted to the Anhui Children's Hospital, Anhui Medical University, from January 2016 to December 2020. Results Of the 16 neonates, there were 13 boys (81%) and 3 girls (19%), with an age of 1 hour to 10 days on admission. Among these neonates, 13 (81%) had cutaneous hemangioma (2 in the head and face, 5 in the trunk, and 6 in the extremities) and 3 (19%) had liver hemangioma. The main clinical manifestations of bleeding tendency and scattered petechiae and ecchymosis were observed in 10 neonates (62%). All the 16 neonates had varying degrees of thrombocytopenia and coagulation disorders. They all received glucocorticoid treatment after admission and 7 (44%) of them had response, among whom 4 experienced recurrence. Among the neonates with no response to glucocorticoid treatment, 3 received sirolimus treatment, among whom 1 had the tumor volume reduced by 58.8% after 4 weeks of treatment, with platelet count and coagulation function returning to normal, while 2 had no significant reduction in tumor volume or significant increase in platelet count and achieved a tumor volume reduced by (43.7±0.4)% after 4 weeks of combined treatment with bleomycin arterial embolization, with platelet count and coagulation function returning to normal. After 4 weeks of bleomycin arterial embolization alone for 4 neonates, tumor volume was reduced by (52.0±3.4)%, and platelet count and coagulation function returned to normal. Blunt and sharp dissection was performed for 2 neonates. The tumor was removed completely during surgery in the 2 neonates, with no infection or recurrence after surgery, and platelet count and coagulation function returned to normal. The postoperative pathological examination showed Kaposiform hemangioendothelioma in 1 out of the 2 neonates. Conclusions KMS has characteristic clinical manifestations, histopathological features, and laboratory examination results. The KMS neonates who are not sensitive to glucocorticoids can achieve a good curative effect through arterial embolization and sirolimus treatment.

Objective To study whether there are differences in the resuscitation process and early outcomes between the extremely preterm infants delivered on off-hours (6 pm to 8 am of working days, weekends, and national holidays) and those delivered on working hours. Methods A retrospective analysis was performed on the medical data of extremely preterm infants who were born in the Peking University Third Hospital from January 1, 2010 to December 31, 2020 and transferred to the neonatal intensive care unit (NICU). According to the time of birth, they were divided into two groups:working hours (n=77) and off-hours (n=98). The resuscitation process and early outcomes were compared between the two groups. Results Compared with the working hours group, the off-hours group had a significantly lower proportion of infants with the use of full-dose dexamethasone before delivery (P < 0.05) and a significantly higher proportion of infants with a 1-minute Apgar score of < 7, positive pressure ventilation, or tracheal intubation (P < 0.05). The incidence rates of neonatal respiratory distress syndrome and intrauterine pneumonia in the off-hours group were significantly higher than those in the working hours group (P < 0.05). Conclusions Extremely preterm infants delivered on off-hours tend to have a low Apgar score at 1 minute after birth, with a higher proportion of infants requiring positive pressure ventilation or tracheal intubation during resuscitation than those delivered on working hours, and they tend to develop neonatal respiratory distress syndrome and intrauterine pneumonia. This suggests that it is important to make adequate preparations in terms of personnel and supplies for resuscitation of extremely preterm infants after birth and that NICUs should develop a detailed management plan for extremely preterm infants at each period of time before, during, and after birth.

Objective To study the drug resistance of Mycoplasma pneumoniae (MP) in the bronchoalveolar lavage fluid (BALF) of children with refractory Mycoplasma pneumoniae pneumonia (RMPP) and the distribution of drug-resistance genes, as well as the association of alleles at 2063 locus of 23SrRNA V region central ring with resistance to antimicrobial drugs. Methods BALF specimens were collected from 245 children with RMPP who were admitted to the Children's Hospital Affiliated to Zhengzhou University from March 2016 to December 2020. A rapid cultured drug sensitivity assay was used to detect the resistance of MP isolates to nine commonly used antimicrobial drugs. The real-time PCR was used to measure MP DNA. The direct sequencing was used to detect gene mutations in MP 23SrRNA V region central ring. Results Among the 245 BALF specimens, 207 tested positive for MP DNA, with a positive rate of 84.5%. The results of drug susceptibility test showed that the children with RMPP had a resistance rate of > 70% to macrolide antimicrobial drugs, with the highest resistance rate to clarithromycin, followed by roxithromycin, clindamycin, acetylspiramycin, erythromycin, and azithromycin, and these children had a resistance rate of < 5% to quinolone antimicrobial drugs. Among the 207 MP DNA-positive specimens, 41 (19.8%) had no drug-resistance gene mutations and 166 (80.2%) had drug-resistance gene mutations, among which 154 (74.4%) had an A→G mutation at 2063 locus of 23SrRNA V region central ring, 7 (3.4%) had an A→G mutation at 2064 locus, and 5 (2.4%) had mutations in both 2063 and 2064 loci. Among the 166 specimens with point mutations of the MP 23SrRNA gene, 159 (95.8%) had point mutations at 2063 locus. The A→G point mutation at 2063 locus of 23SrRNA V region central ring had a great impact on resistance to macrolide antimicrobial drugs. There was a significant difference in the distribution of alleles at 2063 locus between the children with resistance to clarithromycin, roxithromycin, clindamycin, acetylspiramycin, erythromycin, and azithromycin (P < 0.05). Conclusions MP in the BALF of children with RMPP has a relatively high resistance rate to macrolide antimicrobial drugs. Resistance to macrolide antimicrobial drugs is closely associated with the A→G point mutation in the 23SrRNA gene, and the point mutation at 2063 locus of 23SrRNA V region central ring may affect the drug-resistance mechanism of MP.

Objective To study the value of airway pH monitoring in determining the association between chronic cough and laryngopharyngeal reflux (LPR) in children. Methods A total of 274 children with chronic cough who were treated from January 2016 to December 2019 were enrolled. The DX-pH detection system was used to conduct 24-hour airway pH monitoring. The association between chronic cough and LPR was analyzed. Results Among the 274 children, there were 168 boys and 106 girls, with a median age of 62.8 months and a median airway pH value of 7.3. Of all the 274 children, 99 (36.1%) had LPR, and the incidence rate of LPR was 36.9% (62/168) in boys and 34.9% (37/106) in girls (P=0.737). The comparison of the incidence rate of LPR among children aged < 1 year, 1-6 years, and > 6 years showed that the younger children had a significantly higher incidence rate of LPR than the older ones (P=0.003). There was no significant difference in the incidence of LPR between the two groups with chronic cough of unknown etiology and definite etiology. The incidence of chronic cough was positively correlated with that of LPR (r_s=0.861, P < 0.01). Among the 99 children with positive RYAN index, 65 (66%) suffered from simple LPR. Conclusions LPR is highly associated with the development of chronic cough, and airway pH monitoring may be a safe and effective method for the diagnosis of LPR.

Objective To investigate the incidence rates of Clostridium difficile colonization and Clostridium difficile infection (CDI) in children with inflammatory bowel disease (IBD) and the susceptibility factors for CDI in children with IBD. Methods A total of 62 children diagnosed with IBD were enrolled as the IBD group. Forty-two children who attended the hospital due to persistent or chronic diarrhea and were excluded from IBD were enrolled as the non-IBD group. The incidence rate of CDI was compared between the two groups. According to the presence or absence of CDI, the IBD group was subdivided into two groups:IBD+CDI (n=12) and non-CDI IBD (n=50), and the clinical data were collected from the two groups to analyze the susceptibility factors for CDI. Results The IBD group had a significantly higher incidence rate of CDI[19% (12/62) vs 2% (1/42); P < 0.05] than the non-IBD group (P < 0.05). Compared with the non-CDI IBD group, the IBD+CDI group had a significantly longer disease course (P < 0.05), and a significantly higher proportion of children with fever, diarrhea, or abdominal pain (P < 0.05). The IBD+CDI group had significantly higher activity indices of pediatric Crohn's disease, C-reactive protein levels and erythrocyte sedimentation rate than the non-CDI IBD group (P < 0.05). The univariate analysis showed that compared with the non-CDI IBD group, the IBD+CDI group had a significantly higher proportion of children with moderate-to-severe disease, use of glucocorticoids, or treatment with broad-spectrum antibiotics for more than 14 days before diagnosis (P < 0.05). Conclusions The children with IBD have a higher incidence of CDI than those without IBD. Severe disease conditions and use of broad-spectrum antibiotics or glucocorticoids may be associated with an increased incidence of CDI in children with IBD.

Objective To study the clinical features and recurrence factors of myelin oligodendrocyte glycoprotein (MOG) antibody disease in children and the effect of recurrence prevention regimens. Methods A retrospective analysis was performed on the medical data of 41 children with MOG antibody disease who were hospitalized in the Department of Pediatric Neurology, Xiangya Hospital of Central South University, from December 2014 to September 2020. According to the presence or absence of recurrence, they were divided into a monophasic course group (n=19) and a recurrence group (n=22). According to whether preventive treatment for recurrence was given, the children with recurrence were further divided into a preventive treatment group and a non-preventive treatment group. The clinical features were analyzed for all groups, and the annualized relapse rate (ARR) was compared before and after treatment with prevention regimens. Results For these 41 children, acute disseminated encephalomyelitis was the most common initial manifestation and was observed in 23 children (56%). Of the 41 children, 22 (54%) experienced recurrence, with 57 recurrence events in total, among which optic neuritis was the most common event (17/57, 30%). The proportion of children in the recurrence group who were treated with corticosteroids for less than 3 months in the acute phase was higher than that in the monophasic course group (64% vs 32%; P < 0.05). There was no significant difference in the ARR between the preventive treatment and non-preventive treatment groups (P > 0.05). The assessment of preventive treatment regimens for 32 cases showed that the children treated with rituximab or azathioprine had a significant reduction in the ARR during treatment (P < 0.05). Conclusions More than half of the children with MOG antibody disease may experience recurrence. Most children with recurrence are treated with corticosteroids for less than 3 months in the acute phase. Rituximab and azathioprine may reduce the risk of recurrence.

Objective To determine the association of circular RNA (circRNA) and circRNA-microRNA (miRNA) network regulation with brain injury induced by inflammation in preterm mice. Methods Pregnant mice were treated with intraperitoneally injected lipopolysaccharide to establish a preterm mouse model of brain injury induced by inflammation (inflammation preterm group with 3 mice). Preterm mice born to normal pregnant mice by cesarean section were selected as controls (non-inflammation preterm group with 3 mice). The gene microarray technique was used to screen out the circRNAs associated with brain injury in preterm mice. The miRNA target prediction software was used to predict the binding sites between circRNAs and miRNAs and analyze the regulatory mechanism. Results A total of 365 differentially expressed circRNAs were screened out between the inflammation preterm and non-inflammation preterm groups (fold change > 1.5, P < 0.05), among which there were 206 upregulated circRNAs and 159 downregulated circRNAs. Further analysis of the circRNAs with a fold change of > 4 showed that these circRNAs could bind to miRNAs and regulate their activity, thereby regulating the expression of the genes associated with the nervous system. Conclusions Inflammation induces a significant change in the expression profile of circRNAs in the brain tissue of mice, and the change in the expression of circRNAs plays an important role in brain injury induced by inflammation and subsequent brain development in preterm mice.

Objective To summarize the experience in the application of muscle relaxants in the perioperative period in neonates with congenital esophageal atresia-tracheoesophageal fistula (EA-TEF). Methods A retrospective analysis was performed on the medical data of 58 previously untreated neonates with EA-TEF who were treated in the Neonatal Center of Beijing Children's Hospital, Capital Medical University from 2017 to 2019. The incidence rate of anastomotic leak was compared between the neonates receiving muscle relaxants for different durations after surgery (≤ 5 days and > 5 days). The correlation between the duration of postoperative use of muscle relaxants and the duration of mechanical ventilation was evaluated. Results Among the 58 neonates with EA-TEF, 44 underwent surgery, among whom 35 with type III EA-TEF underwent thoracoscopic surgery. Among these 35 neonates, 30 (86%) received muscle relaxants after surgery, with a median duration of 4.75 days, and 6 (18%) experienced anastomotic leak. There was no significant difference in the incidence rate of anastomosis leak between the ≤ 5 days and > 5 days groups (P > 0.05). The duration of postoperative invasive mechanical ventilation was positively correlated with the duration of the use of muscle relaxants (r_s=0.548, P < 0.05). Conclusions Prolonged use of muscle relaxants after surgery cannot significantly reduce the incidence of anastomotic leak, but can prolong the duration of invasive mechanical ventilation in neonates with EA-TEF. Therefore, prolonged use of muscle relaxants is not recommended after surgery.

A girl, aged 7 years, was admitted due to pain in both lower limbs for more than one year. Lumbar MRI showed soft tissue masses in the paravertebral region. Cerebral MRI showed nodular masses in the cavernous sinus at both sides. Chest CT showed high-density nodules in the outer basal segment of the right inferior lobe and the anterior segment of the left upper lobe of the lung. Biopsy of lumbar lesions showed Epstein-Barr (EB) virus-related smooth muscle tumor. Genetic testing showed a de novo mutation, c.725_730delAGAGTA (p.K242_S243del), in the ITK gene. The masses in the lumbar vertebra were removed by surgery, and then the pain in both lower limbs disappeared. This article reports a case of EB virus-related smooth muscle tumor with a deletion mutation in the ITK gene, which provides experience for the diagnosis and treatment of this disease.

Gene editing is an advanced technique based on artificial nucleases and can precisely modify genome sequences. It has shown great application prospects in the field of medicine and has provided a new precision therapy for diseases. Primary immunodeficiency disease is a group of diseases caused by single gene mutation and characterized by recurrent and refractory infections, with an extremely high mortality rate. The application of gene editing has brought hope for curing these diseases. This article reviews the development of gene editing technology and briefly introduces the research and application of gene editing technology in primary immunodeficiency disease.

Febrile seizures are the most common nervous system disease in childhood, and most children have a good prognosis. However, some epilepsy cases are easily induced by fever and are characterized by "fever sensitivity", and it is difficult to differentiate such cases from febrile seizures. Epilepsy related to fever sensitivity includes hereditary epilepsy with febrile seizures plus, Dravet syndrome, and PCDH19 gene-related epilepsy. This article mainly describes the clinical manifestations of these three types of epilepsy and summarizes their clinical features in the early stage of disease onset, so as to achieve early identification, early diagnosis, and early intervention to improve prognosis.

Adequate supply of long-chain polyunsaturated fatty acids (LCPUFAs) is of great importance for neonates, especially preterm infants. In particular, n-3 LCPUFAs and n-6 LCPUFAs play a key role in brain development, immune regulation, and disease prevention. Lack of LCPUFAs may lead to neurodevelopmental impairment, affect the development of neonatal immune system, and result in neonatal diseases. This article reviews related research advances in the physiological function of LCPUFAs and its effect on neonates, so as to provide reference for clinical application.